Dr Anna Meta Dyrvig Kristensen

My name is Anna Meta Kristensen and I'm a medical doctor at Bispebjerg and Frederiksberg University Hospital in Denmark.

What prompted this collaborative meta-analysis across multiple beta-blocker trials in post-MI patients?

We started collaborating when the trials were ongoing as we knew that none of the trials were sufficiently powered to assess individual outcomes and lacked data for robust subgroup analysis. And furthermore, the trials had different primary endpoints and their results were a little bit divergent. So therefore, we believed and believed that meta-analysis consolidating the totality of evidence from randomised trials on beta-blockers were essential.

Can you describe the included trials and the overall patient population analysed?

Yes, if we start with the included trials, we included five contemporary beta-blocker trials: the Spanish-Italian REBOOT trial, the Swedish REDUCE trial, the Norwegian BETAMI, and the Danish DANBLOCK, and lastly the Japanese CAPITAL-RCT trial.

And all of these trials were investigator-initiated, open-label, randomised, superiority trials. And all of the trials had independent adjudication of their endpoints, except the REDUCE-AMI trial. And all of these trials included patients with a recent MI, with either mildly reduced or preserved LVEF, except the REDUCE-MI trial, which only included patients with preserved LVEF. And these patients had no indications nor contraindications to beta-blocker therapy, and they were randomised to either beta-blocker therapy or no beta-blocker therapy.

So that's a little bit about the included trials. And if we focus on the patient population of this meta-analysis, we included a total of 17,801 patients from these trials, and the median age was 62 years. 21% were women and a little bit less than half of the population had had a STEMI.

And if we look at the patients randomised to beta blockers then 47% were treated with bisoprolol and 46% with metoprolol. And maybe it might be important to add that the vast, vast majority, 96% of the patient population, were revascularized.

What were the key findings regarding clinical outcomes with beta-blocker therapy in this population?

Yes, in this patient population were patients with a recent MI and preserved LVEF. And we found that beta-blockers did not reduce the incidence of a composite of death, MI, or heart failure. The hazard ratio was 0.97, and the p-value was 0.54. The results were consistent across the individual components of the primary endpoint, across the other endpoints, across trials, and across pre-specified sensitivity analysis.

And if we look at the subgroups included in the trial, they were pre-specified subgroups, we found the same results. There appeared to be neither benefit nor harm in any of the included subgroups, including age, sex, type of MI, previous beta-blocker therapy, et cetera.

How should these findings influence clinical decision-making for beta-blocker prescribing after MI?

That's a very important question, and I think I need to stress that all patients should be assessed on an individual level. And our findings do not support routine withdrawal of beta-blockers for all patients with preserved LVEF after MI. Actually, a substantial proportion of patients were ineligible to be included in the trials because of an existing indication for beta-blockers such as atrial fibrillation, heart failure, uncontrolled hypertension.

However, we believe that it is important, especially in this era of increasing polypharmacy, to evaluate whether we should be treating patients with all of the medication that we do. And our findings does not support routine beta-blocker therapy to all patients. And to help guide the clinicians, we're actually also currently working on sub-studies focusing on patient-related outcomes and physical activities, etc.

What are the implications for current guideline recommendations?

Together with our recently published meta-analysis on patients with mild LVEF. I think we or I believe that this study provides valuable insights to inform clinical practise and guideline recommendations on beta-blockers after MI. And the beneficial effects of beta-blockers in patients with mildly reduced LVEF aligns well with the current recommendations and the recommendations for patients with heart failure.

But our findings do not support routine prescription of beta-blockers for all MI patients with preserved LVEF. But ultimately, it's up to the clinical community and the guideline committees to make recommendations that balance safety and efficacy and patient-related outcomes.